Short-term in vitro Inhibition of Glycogen

Type 2 diabetes mellitus (T2D) is the most common form of diabetes (American Diabetes Association, 2012). T2D is so prevalent that it is estimated to be the fifth most common cause of death worldwide (Yates, Jarvis, Troughton, and JaneDavies, 2009, p. 1). T2D manifests when the body is unable to metabolize glucose properly, resulting in elevated blood sugar, debilitating fatigue, and other serious complications such as distal limb amputations, kidney failure, and blindness. The generally accepted causes of T2D include diet, sedentary lifestyle, and obesity.

Diabetes is a growing concern and health challenge for the American people (b). Diabetes is a condition in which the body cannot react to insulin appropriately or either cannot produce insulin efficiently (w). “Without a properly functioning insulin signaling system, blood glucose levels become elevated and other metabolic abnormalities occur, leading to the development of serious, disabling complications” (w). There are numerous forms of diabetes amongst the nation, however, there are three main forms of diabetes. Most people have heard of type one diabetes, type two diabetes, and gestational diabetes because they are common. Type two diabetes deals with a resistance to insulin, while

Insulin resistance is the first physiological change occurring in type two diabetes. In these type two diabetic patients, insulin is unable to move glucose into liver, kidney and muscle cells although insulin is able to attach properly to the cell surface receptors. In order to rectify this, most patients with type two diabetes start secreting normal to very high levels of insulin, which can initially overcome this resistance. After a while, the pancreas cannot keep up with this high insulin production and the cells become resistant to glucose intake. Persistent hyperglycemia or high blood glucose levels are not desirable since this causes damage to the beta cells of the pancreas that produces the insulin hormone. This damage to beta cells further hampers insulin synthesis and patients at this stage are categorized as full-blown diabetic. Such patients consistently show a hyperglycemia state even after hours of fasting ( Hinkle & Cheever,

For determination of oxidative stress and insulin response, C2C12 murine myoblasts, grown with approximately 90% confluence, were induced for differentiation and placed into myotubes. Primary muscle cells taken from mice were isolated for growth and differentiation. Human cells were collected from 10 subjects consisting of 5 lean and 5 overweight females.

This paper aims to provide the gaps in our understanding of the Type 2 Diabetes by examining the functions of the pancreas in controlling the sugar levels in the human body and enhance our ability to distinguish the anatomy of the human pancreas. The author also attempts a better understanding of the function of insulin and glucagon hormones in the pancreatic process. It is hoped that this paper will inform those who do not have the understanding and knowledge about the signs and symptoms, causes, treatments, care and prevention of the Type 2 Diabetes.

Type II Diabetes is a disease that is mostly manageable, despite the recent surge in diagnoses. Type II diabetes is generally a controllable and preventable condition, but in the case of extreme obesity, is difficult to manage. The connection between extreme obesity and the inevitable insulin resistance of the body is widely known throughout the population. The problem is real and it is thoroughly documented by research institutions around the world. Type II Diabetes develops when insulin secretion cannot keep the body at normal glycemic levels, causing insulin secretion and tissues that do not respond properly to the insulin that is being secreted.

The researchers demonstrated that human liver cells would secrete insulin as well as control blood glucose levels in vivo by testing diabetic immunedeficient mice. They observed how well a mouse would improve the state of hyperglycemia. They observed the immunodeficient mice before and during the times of the study to attribute the change in the glucose blood levels were due to the liver

Type 2 diabetes results from a multitude of defects: impaired insulin secretion, insulin resistance, and defects in GLP-1 secretion and action. Prior to the onset and throughout the course of the disease, beta cell function and pancreatic mass deteriorate; causes may be lipotoxicity, glucose toxicity, increased age, genetics, insulin resistance, and incretin deficiency. Insulin resistance takes place in the liver, adipose, and skeletal tissues (1), ultimately leading to decreased peripheral uptake and hyperglycemia. In the liver, lack of insulin action results in gluconeogenesis and glycogenolysis, further potentiating the hyperglycemia. In fat cells, decreased GLUT4 leads to excessive release of free fatty acids and adipocytokines (2). Because

Insulin resistance is a fundamental aspect of Type 2 diabetes. Insulin lowers blood glucose by suppressing liver glucose production and increases glucose uptake into muscle and fat cells. The majority of glucose gets largely stored in the muscle and adipose tissue contributes little to glucose disposal. Insulin is a critical regulator of adipocytes as it promotes adipocyte triglyceride storage by helping preadipocytes get differentiated to adipocytes. Adipocytes are over 1 billion cells that specialize storing energy as fat and together they constitute the largest endocrine system that communicates to other tissues by adipocyte-released secretagogues including proteohormones lectin, adiponectin, and visfatin. (Redinger, R., 2007) Along

These tissues are insulin-sensitive and respond to increased blood insulin levels by a rapid and reversible increase in glucose transport (Abel et al., 2001). Abel et al. suggest that this is brought about by the translocation of a latent pool of glucose transporters from an intracellular site to the plasma membrane (2001). In the absence of insulin, GLUT4 storage vesicles might slowly fuse with endosomes, vesicles in the red blood cell (Kraegen et al., 1993). Insulin would then shift GLUT4 from this cycle to a pathway that takes GLUT4 directly to the cell surface (Abel et al., 2001). Glucose uptake into muscle and adipose tissue is transported by GLUT4 is promoted by insulin based on the need for glucose in the tissue. In response to insulin, the pancreas senses the hyperglycemic state in tissues and releases insulin for uptake of

Up regulation of insulin secretion take place in pancreas. Insulin is secreted in reaction to elevated blood concentrations of glucose. Insulin and its signaling systems are involved in both central and peripheral mechanisms of the nervous system, prevailing the ingestion, distribution, metabolism, and storage of nutrients in organisms ranging from animals to humans2. Increasing evidences shows that in the central nervous system, reduced insulin, adds to the pathogenesis of common metabolic disorders, including diabetes and obesity. These deliberations involve insulin

(Hermanns-Le, Scheen, & Pierard, 2014, p. 200) As our cells fail to respond to insulin, the beta cells of the pancreas produce more insulin and trigger the liver to produce more glucose to restore glycemic control. This compensational mechanism will eventually be unable to keep up with the body’s demands leading to elevated glucose levels in circulation. Eventually, the high demand of pancreatic beta cells to produce insulin will not be able to keep up and insulin production will become insufficient, lessening the uptake of glucose. This now opens the path to Type II Diabetes Mellitus. (Thoenes, 2012, p. 621)

When muscle is damaged, there is a general resistance to insulin. The physiological stress that is associated with damaged muscle impairs how insulin stimulates IRS-1, PI 3-kinase, and Akt-kinase. This presumably leads to less glucose absorption. Previous studies have shown that there has been temporary insulin resistance due to the physiological stress associated with muscle damage. However, the molecular mechanisms by which physiological stress induces insulin resistance is not known.

(Donato, et al., 2013) Nevertheless, the proteins S100A9, S100A12 are the ones that have shown an important effect in the pathology of diabetes. There have been studies of the expression and circulation of S100A9 in muscle cells, adipose tissue and isolated fat cell in mice, as well as in human models. (Ortega, et al., 2013). These studies showed a higher expression as well as circulation in high glucose conditions, created by Diabetes type II, which demonstrate the influence of this molecule in the pathology of Diabetes. (Ortega, et al., 2013). Another important molecule in diabetes pathology is the protein S100A2. (Kosaki et al., 2004) In fact, there are studies that shows that the concentrations of these protein is twice as high in the patients with diabetes (Diabetes type II), compared with those without, which demonstrate the importance of this molecule in this disease. (Kosaki et al.,

Diabetes Mellitus is a debilitating and chronic disease in which life long care and rehabilitation is required. According to the World Health Organization, diabetes affects over 300 million people worldwide, and continues to rise each year. There are three main categories of diabetes; type 1, type 2 and gestational diabetes. The pathophysiology of diabetes mellitus is related to insulin, which is a hormone secreted by the cells of the pancreas. (WHO) Insulin is responsible for maintaining an ideal glucose level in the blood. Due to abnormal insulin metabolism, the cells and tissues can’t make use of glucose from the blood, resulting in elevated blood glucose levels. (WHO)